双特异性磷酸酶 18 调节 Ataxin-1 的 SUMOylation 和聚集。
Dual-specificity phosphatase 18 modulates the SUMOylation and aggregation of Ataxin-1.
机构信息
Department of Cellular and Molecular Biology, The Hormel Institute, University of Minnesota, Austin, MN, USA.
Department of Biotechnology, Seoul Women's University, Seoul, South Korea.
出版信息
Biochem Biophys Res Commun. 2018 Jul 20;502(3):389-396. doi: 10.1016/j.bbrc.2018.05.178. Epub 2018 May 31.
We previously reported that SUMOylation promotes the aggregation of ataxin-1 and JNK is involved in the process. Here we show that dual-specificity phosphatase 18 (DUSP18), a member of protein tyrosine phosphatases, exerts the opposite effects on ataxin-1. DUSP18 associated with ataxin-1 and suppressed JNK activated by ataxin-1. Interestingly DUSP18, but not the other DUSPs interacting with ataxin-1, caused the mobility shift of ataxin-1. De-phosphorylation by DUSP18 was initially suspected as a cause for such an effect; however, the phosphorylation of ataxin-1 was unchanged. Instead DUSP18 inhibited SUMOylation and reduced ataxin-1 aggregation. The catalytic mutant of DUSP18 failed to reduce the SUMOylation and aggregation of ataxin-1 indicating that the phosphatase activity is indispensable for the effects. Moreover, DUSP18 disrupted the co-localization of ataxin-1 with the PML component Sp100. These results together implicate that JNK and DUSP18 reciprocally modulate the SUMOylation, which plays a regulatory role in the aggregation of ataxin-1.
我们之前报道过，SUMOylation 促进了共济失调蛋白 1（ataxin-1）的聚集，而 JNK 参与了这一过程。在这里，我们发现双特异性磷酸酶 18（DUSP18），一种蛋白酪氨酸磷酸酶的成员，对 ataxin-1 产生相反的影响。DUSP18 与 ataxin-1 结合，并抑制了由 ataxin-1 激活的 JNK。有趣的是，DUSP18（而不是与 ataxin-1 相互作用的其他 DUSPs）导致了 ataxin-1 的迁移率改变。最初怀疑 DUSP18 的去磷酸化是这种效应的原因；然而，ataxin-1 的磷酸化没有改变。相反，DUSP18 抑制了 SUMOylation 并减少了 ataxin-1 的聚集。DUSP18 的催化突变体未能减少 ataxin-1 的 SUMOylation 和聚集，表明其磷酸酶活性对于这些效应是必不可少的。此外，DUSP18 破坏了 ataxin-1 与 PML 成分 Sp100 的共定位。这些结果共同表明，JNK 和 DUSP18 相互调节 SUMOylation，这在 ataxin-1 的聚集中发挥了调节作用。
Zotero 插件